熊果酸磷脂复合物纳米结构脂质载体的制备及其体内药动学研究

Preparation and in vivo pharmacokinetics of nanostructured lipid carriers of ursolic acid phospholipids complex

目的制备熊果酸磷脂复合物纳米结构脂质载体,并考察其体内药动学。方法乳化⁃超声分散法制备熊果酸磷脂复合物纳米结构脂质载体,测定粒径、Zeta电位、包封率、载药量、体外释药。大鼠灌胃给药(12.5 mg/mL)后,于0.25、0.75、1、1.5、2、2.5、3、4、6、8、12 h采血,HPLC法测定熊果酸血药浓度,计算主要药动学参数。结果所得制剂呈类球形或球形,平均粒径、Zeta电位、包封率、载药量分别为(209.32±4.47)nm、-(10.82±0.42)mV、80.54%、3.57%;36 h内累积释放度低于70%,释药符合Weibull模型(R2=0.9906)。与原料药、磷脂复合物比较,纳米结构脂质载体tmax延长(P<0.05,P<0.01),Cmax、AUC0~t、AUC0~∞升高(P<0.01);与原料药比较,磷脂复合物、纳米结构脂质载体相对生物利用度分别增加至2.73、3.95倍。结论磷脂复合物纳米结构脂质载体可促进熊果酸体内吸收,提高其口服生物利用度。

AIM To prepare the nanostructured lipid carriers of ursolic acid phospholipids complex and to investigate the in vivo pharmacokinetics.METHODS For the nanostructured lipid carriers of ursolic acid phospholipids complex prepared by emulsification⁃ultrasonic dispersion method,the particle size,Zeta potential,encapsulation efficiency and drug loading were determined.Rats were given intragastric administration(12.5 mg/mL),after which blood collection was made at 0.25,0.75,1,1.5,2,2.5,3,4,6,8,12 h,then HPLC was adopted in the plasma concentration determination of ursolic acid,and main pharmacokinetic parameters were calculated.RESULTS The obtained spherical⁃like or spherical preparation demonstrated the average particle size,Zeta potential,encapsulation efficiency and drug loading of(209.32±4.47)nm,-(10.82±0.42)mV,80.54%,3.57%,respectively,whose accumulative release rate was less than 70%within 36 h,and drug release accorded with Weibull model(R2=0.9906).Compared with the raw medicine and phospholipids complex,the nanostructured lipid carriers displayed prolonged tmax(P<0.05,P<0.01)and increased Cmax,AUC0-t and AUC0-∞(P<0.01),the relative bioavailabilities of phospholipids complex,nanostructured lipid carriers were enhanced to 2.73,3.95 times as compared with that of the raw medicine,respectively.CONCLUSION The nanostructured lipid carriers of phospholipids complex can improve the in vivo absorption of ursolic acid and enhance its oral bioavailability.